Ivermectin pharmacokinetics

The pharmacokinetics of ivermectin differ with the animal species, formulation, and the route of administration (50). When goats were given a subcutaneous administration of 0.2 mg ivermectin /kg bw, the mean concentrations of ivermectin in plasma and milk increased initially to reach at 2.8 day the maximum levels of 6.12 and 7.26 ppb, respectively (51). The drug could be detected in milk for 25 days postdosing, the total drug amount recovered over this period being estimated at 0.6% of the administered dose. This percentage is low compared with the 4% level determined in sheep (52) and 5.6% in cows (53). 

Goa KL, McTavish D, Clissold SP. Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 1991 42 640-658. 

Table 5 Pharmacokinetic parameters describing the rate of absorption and elimination of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD) after subcutaneous injection (shoulder region) of single doses (200 pg/kg) of the commercially available preparations to 10-month-old hereford calves...

Emesis, ataxia, and mydriasis are cardinal signs of ivermectin toxicity. The safety, tolerability, and pharmacokinetics of escalating high-dose ivermectin have been studied in 68 healthy subjects in a randomized, doubleblind, placebo-controlled study (21) in the following doses ... 

Guzzo CA, Furtek Cl, Porras AG, Chen C, Tipping R, Clineschmidt CM, Sciberras DG, Hsieh JY, Lasseter KC. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol 2002 42(10) 1122-33. 

Taylor Kenny 1995, DiPietro et al 1997, Demeulenaere et al 1997). However, while there are significant differences in the pharmacokinetic profile (longer plasma residence time and higher peak plasnu concentrations) following oral dosing with commercial preparations of moxidectin and ivermectin, this may also reflect differences in the product formulation (oral gel versus oral paste) and manufacturer s recommended dose rates (0.4mg/kg versus 0.2mg/kg) as well as the different lipophilicity of the two compounds (Perez et al 1999). 

Paterson S, Orrell S 1995 Treatment of biting lice (Damalinia equi) in 25 horses using 1 % selenium sulphide. Equine Veterinary Education 7 304-306 Pereira M C, Kohek I Jr, Campos R et al 1991 A field evaluation of antheimintics for control of cyathostomes of horses in Brazil. Veterinary Parasitoiogy 38 121-129 Perez R, Cabezas i, Garcia M et al 1999 Comparison of the pharmacokinetics of moxidectin (Equest ) and ivermectin (Eqvalan ) in horses. Journai of Veterinary Pharmacology and Therapeutics 22 174-180... 

The idiosyncratic toxicity, manifested by neurological effects, shown by a subpopulation of (rough-haired) Collies to ivermectin (> 100 gg/kg, p.o.) may be attributed to a breed-related compromised blood-brain barrier (Tranquilli et al, 1989), since y-aminobutyric acid receptors that mediate neurotransmission are confined to the CNS in mammalian species. The pharmacokinetic behaviour of ivermectin does not differ between ivermectin-sensitive and... 

Ali, D.N. Hennessy, D.R. (1996) The effect of level of feed intake on the pharmacokinetic disposition and efficacy of ivermectin in sheep. Journal of Veterinary Pharmacology and Therapeutics, 19, 89-94. 

No pharmacokinetic interaction occurs between albendazole and ivermectin. 

Awadzi K, Edwards G, Duke BOL, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quarty BT. The co-administration of ivermectin and albendazole— safety, pharmacokinetics and efficacy t Onchocerca volvulus Ann TropMedParasitol(2003) 97,165-78. 

Levamisole may markedly increase the bioavailability of ivermectin. Ivermectin does not alter the pharmacokinetics of levamisole. 

Numerous transporter knockout animals are available to evaluate pharmacokinetic distribution of NCEs. Schinkel et al. (1994) generated the knockout mdrla (P-gp) mouse model that became 100-fold more sensitive to the neurotoxic pesticide ivermectin. This classic model has demonstrated how critical P-gp is to preventing xenobiotics from crossing the BBB (Loscher and Potschka, 2005 Kusuhara and Sugiyama, 2005 Terasaki and Ohtsuki, 2005 ... 

Kazan L, Berg JE, Bowman JP, Murray JV, Ryan WG. Pharmacokinetics and safety of 0.5% ivermectin lotion for head Louse infestations. Pediatr Dermatol 2013 30(3) 323-8. 

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